The short ragweed is a major offending agent in clinical pollinosis in the United States and Canada. Several important protein allergens have been isolated from the pollen of this plant (Ambrosia eletior) and a considerable body of evidence indicates that human sensitivity to these allergens may depend on the possession of certain histocompatibility antigens. Our laboratory, in collaboration with Dr. Lawrence Goodfriend, has recently completed the total amino acid sequence of Ra5, one of the low molecular weight pollen allergens. As an initial goal of these studies we plan to obtain small fragments of this allergen in hopes of separating the carrier-active fragments from the allergenically and antigenically active fragments of the molecule. Secondly, we hope to deduce the disulfide bond structure of the Ra5 molecule. A second, and perhaps more important allergen in this group is Ra3, a 100 amino acid residue protein with potent biological properties. The genetics of the immune response to this allergen are just being worked out and knowledge of its structure will be important in understanding the relationships between structure, genetics, and response between Ra3 and Ra5. A longer range goal of these studies would be the synthesis of certain portions of these molecules as potential therapeutic agents.